Selective autoantibody production against CCL3 is associated with human type 1 diabetes mellitus and serves as a novel biomarker for its diagnosis

Naim Shehadeh, Shirly Pollack, Gizi Wildbaum, Yaniv Zohar, Itay Shafat, Reem Makhoul, Essam Daod, Fahed Hakim, Rina Perlman, Nathan Karin

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

We have recently demonstrated that patients suffering from chronic autoimmune diseases develop an autoantibody response against key mediators that participate in the initiation and progression of these diseases. In this paper, we show that patients with type 1 diabetes mellitus (T1DM), but not those suffering from several other inflammatory autoimmune diseases, display a selective autoantibody titer to a single CC chemokine named CCL3. From the diagnostic point we show that this response could be used as a biomarker for diagnosis of T1DM, a disease that is currently diagnosed by autoantibodies to competitive anti-insulin Abs, islet cell Abs, and glutamic acid decarboxylase Abs. We show that our currently suggested biomarker is more reliable than each of the above alone, including diagnosis of T1DM at its preclinical stage, and could therefore be used as a novel way for diagnosis of T1DM. These Abs were found to be neutralizing Abs. It is possible, though hard to prove, that these Abs participate in the natural regulation of the human disease. Hence, it has previously been shown by others that selective neutralization of CCL3 suppresses T1DM in NOD mice. Theses results together with ours suggest CCL3 as a preferential target for therapy of T1DM.

Original languageEnglish
Pages (from-to)8104-8109
Number of pages6
JournalJournal of Immunology
Volume182
Issue number12
DOIs
StatePublished - 15 Jun 2009
Externally publishedYes

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